Microbial Resistance
Increasing incidence of microbial resistance to antibiotics and other antimicrobials is a growing concern facing the medical, food and sanitation industries. Major mechanisms of microbial resistance include active drug efflux systems and mutations which lead to nonspecific decreases in cell permeability. Other routes to resistance include antimicrobial degradation, inactivation by enzymatic modifications, or alteration of the drug's target within the cell (Nikkaido, 1994).
To counter the increasing incidence of antimicrobial resistance, the pharmaceutical and other industries have invested substantial resources in the search for new inhibitory compounds of microbial, plant and animal origin. Newer strategies to overcome antimicrobial resistance have included increased production of new synthetic and semisynthetic antibiotics which are resistant to the activities of those microbial enzymes (i.e. .beta.-lactamases) capable of degradation or modification of naturally-derived antibiotics (Nikkaido, 1994).
Although many specific mechanisms of microbial resistance have been successfully addressed, it is thought that the more general mechanisms of altered permeability and increased efflux capability will become increasingly important from a clinical perspective (Nikkaido, 1994).
Efflux systems and mechanisms of antibiotic degradation rely on saturable biological structures (i.e., pumps or enzymes). If the nonspecific influx of an intracellularly or membrane-targeted lethal agent is high enough to overcome these inactivation mechanisms, then the effect of these mechanisms might be minimized, leading to the death of the cell.
Terpenoids
Terpenoids, a broad class of lipophilic secondary metabolites derived from mevalonate and isopentenyl pyrophosphate, occur widely in nature and have been of historical interest to man primarily for their contribution to the characteristic flavors and aromas of herbs, spices and flowers. As of 1991, the number of recognized natural terpenoids had reached an estimated 15,000 to 20,000 (Harborne, 1991).
Sesquiterpenoid compounds, containing 15 carbons, are formed biosynthetically from three 5-carbon isoprene units. Because of their naturally pleasing odors and flavors, many sesquiterpenoids of plant origin have found use in perfumery and flavoring applications and are now produced industrially from monoterpenoid feedstock. For example, nerolidol, commonly used to provide a base note for floral aroma compositions, is readily produced from linalool, itself derived from .alpha.-pinene, which occurs in high concentration in turpentine oil (Bauer, et al., 1997).
Apart from their use in perfumery, terpenoids have been associated with a variety of important biological functions as pheromones, insect antifeedants, phytoalexins and others (Harborne, 1991).